Abstract: ObjectiveThe International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system classifies gestational trophoblastic neoplasia (GTN) patients into low- and high-risk groups, so that single- or multi-agent chemotherapy can be administered accordingly. However, a number of FIGO-defined low-risk patients still exhibit resistance to single-agent regimens, and the risk factors currently adopted in the FIGO scoring system possess inequable values for predicting single-agent chemoresistance. The purpose of this study is therefore to evaluate the efficacy of risk factors in predicting single-agent chemoresistance and explore the feasibility of simplifying the FIGO 2000 scoring system for GTN.
MethodsThe clinical data of 578 GTN patients who received chemotherapy between January 2000 and December 2018 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were carried out to identify risk factors associated with single-agent chemoresistance in low-risk GTN patients. Then, simplified models were built and compared with the original FIGO 2000 scoring system.
ResultsAmong the eight FIGO risk factors, the univariate and multivariate analyses identified that pretreatment serum human chorionic gonadotropin (hCG) level and interval from antecedent pregnancy were consistently independent predictors for both first-line and subsequent single-agent chemoresistance. The simplified model with two independent factors showed a better performance in predicting single-agent chemoresistance than the model with the other four non-independent factors. However, the addition of other co-factors did improve the efficiency. Overall, simplified models can achieve favorable performance, but the original FIGO 2000 prognostic system still features the highest discrimination.
ConclusionsPretreatment serum hCG level and interval from antecedent pregnancy were independent predictors for both first-line and subsequent single-agent chemoresistance, and they had greater weight than other non-independent factors in predicting single-agent chemoresistance. The simplified model composed of certain selected factors is a promising alternative to the original FIGO 2000 prognostic system, and it shows comparable performance.

妊娠滋养细胞肿瘤单药化疗疗效影响因素分析及FIGO2000预后评分系统简化

[1]AbrãoRA, de AndradeJM, TiezziDG, et al., 2008. Treatment for low-risk gestational trophoblastic disease: comparison of single-agent methotrexate, dactinomycin and combination regimens. Gynecol Oncol, 108(1):149-153.

[2]BagshaweKD, 1976. Risk and prognostic factors in trophoblastic neoplasia. Cancer, 38(3):1373-1385.https://doi.‍org/10.1002/1097-0142(197609)38:‍3<1373::aid-cncr2820380342>3.0.co;2-e

[3]BragaA, PaivaG, GhoraniE, et al., 2021. Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study. Lancet Oncol, 22(8):1188-1198.

[4]ChalouhiGE, GolfierF, SoignonP, et al., 2009. Methotrexate for 2000 FIGO low-risk gestational trophoblastic neoplasia patients: efficacy and toxicity. Am J Obstet Gynecol, 200(6):643.e1-643.e6.

[5]Chapman-DavisE, HoekstraAV, RademakerAW, et al., 2012. Treatment of nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia: factors associated with resistance to single-agent methotrexate chemotherapy. Gynecol Oncol, 125(3):572-575.

[6]CyriacS, RajendranathR, SrideviV, et al., 2011. Etoposide, cisplatin-etoposide, methotrexate, actinomycin-D as primary treatment for management of very-high-risk gestational trophoblastic neoplasia. Int J Gynecol Obstet, 115(1):37-39.

[7]EysboutsYK, OttevangerPB, LFAGMassuger, et al., 2017. Can the FIGO 2000 scoring system for gestational trophoblastic neoplasia be simplified? A new retrospective analysis from a nationwide dataset. Ann Oncol, 28(8):‍1856-1861.

[8]FIGO Oncology Committee, 2002. FIGO staging for gestational trophoblastic neoplasia 2000. Int J Gynaecol Obstet, 77(3):285-287.

[9]GleesonNC, FinanMA, FioricaJV, et al., 1993. Nonmetastatic gestational trophoblastic disease. Weekly methotrexate compared with 8-day methotrexate-folinic acid. Eur J Gynaecol Oncol, 14(6):461-465.

[10]GrowdonWB, WolfbergAJ, GoldsteinDP, et al., 2010. Low-risk gestational trophoblastic neoplasia and methotrexate resistance: predictors of response to treatment with actinomycin D and need for combination chemotherapy. J Reprod Med, 55(7-8):279-284.

[11]HancockBW, 2003. Staging and classification of gestational trophoblastic disease. Best Pract Res Clin Obstet Gynaecol, 17(6):869-883.

[12]HoeijmakersYM, FCGJSweep, LokCAR, et al., 2020. Risk factors for second-line dactinomycin failure after methotrexate treatment for low-risk gestational trophoblastic neoplasia: a retrospective study. BJOG, 127(9):1139-1145.

[13]JiangF, WanXR, XuT, et al., 2018. Evaluation and suggestions for improving the FIGO 2000 staging criteria for gestational trophoblastic neoplasia: a ten-year review of 1420 patients. Gynecol Oncol, 149(3):539-544.

[14]KangWD, KimCH, ChoMK, et al., 2010a. Serum hCG level and rising world health organization score at second-line chemotherapy (pulse dactinomycin): poor prognostic factors for methotrexate-failed low-risk gestational trophoblastic neoplasia. Int J Gynecol Cancer, 20(8):1424-1428.

[15]KangWD, ChoiHS, KimSM, 2010b. Weekly methotrexate (50 mg/m²) without dose escalation as a primary regimen for low-risk gestational trophoblastic neoplasia. Gynecol Oncol, 117(3):477-480.

[16]KohornEI, 2002. Negotiating a staging and risk factor scoring system for gestational trophoblastic neoplasia. A progress report. J Reprod Med, 47(6):445-450.

[17]LeJ, XieX, LinZQ, et al., 2007. Gynaecology and Obstetrics, 7nd Ed. People’s Medical Publishing House, Beijing, China(in Chinese).

[18]LertkhachonsukAA, IsranguraN, WilailakS, et al., 2009. Actinomycin D versus methotrexate-folinic acid as the treatment of stage I, low-risk gestational trophoblastic neoplasia: a randomized controlled trial. Int J Gynecol Cancer, 19(5):985-988.

[19]LurainJR, 2003. Pharmacotherapy of gestational trophoblastic disease. Expert Opin Pharmaco, 4(11):2005-2017.

[20]LurainJR, ElfstrandEP, 1995. Single-agent methotrexate chemotherapy for the treatment of nonmetastatic gestational trophoblastic tumors. Am J Obstet Gynecol, 172(2 Pt 1):574-579.

[21]LurainJR, Chapman-DavisE, HoekstraAV, et al., 2012. Actinomycin D for methotrexate-failed low-risk gestational trophoblastic neoplasia. J Reprod Med, 57(7-8):283-287.

[22]McgrathS, ShortD, HarveyR, et al., 2010. The management and outcome of women with post-hydatidiform mole ‘low-risk’ gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l^-1. Br J Cancer, 102(5):810-814.

[23]MillerAB, HoogstratenB, StaquetM, et al., 1981. Reporting results of cancer treatment. Cancer, 47(1):207-214.

[24]MoraPAR, SunSY, VelardeGC, et al., 2019. Can carboplatin or etoposide replace actinomycin-D for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia? Gynecol Oncol, 153(2):277-285.

[25]MousaviAS, ZamaniA, KhorasanizadehF, et al., 2015. Resistance to single-agent chemotherapy and its risk factors in low-risk gestational trophoblastic neoplasms. J Obstet Gynaecol Res, 41(5):776-783.

[26]NganHYS, SecklMJ, BerkowitzRS, et al., 2018. Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet, 143(Suppl 2):79-85.

[27]OsborneRJ, FiliaciV, SchinkJC, et al., 2011. Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study. J Clin Oncol, 29(7):825-831.

[28]ProuvotC, GolfierF, MassardierJ, et al., 2018. Efficacy and safety of second-line 5-day dactinomycin in case of methotrexate failure for gestational trophoblastic neoplasia. Int J Gynecol Cancer, 28(5):1038-1044.

[29]SecklMJ, SebireNJ, BerkowitzRS, 2010. Gestational trophoblastic disease. Lancet, 376(9742):717-729.

[30]SmithEB, WeedJC, TyreyL, et al., 1982. Treatment of nonmetastatic gestational trophoblastic disease: results of methotrexate alone versus methotrexate-folinic acid. Am J Obstet Gynecol, 144(1):88-92.

[31]SongHZ, YangXY, XiangY, 2004. Trophoblastic Tumor Diagnosis & Treatment, 2nd Ed. People’s Medical Publishing House, Beijing, China(in Chinese).

[32]SoperJT, EvansAC, ConawayMR, et al., 1994. Evaluation of prognostic factors and staging in gestational trophoblastic tumor. Obstet Gynecol, 84(6):969-973.

[33]SungHC, WuPC, YangHY, 1984. Reevaluation of 5-fluorouracil as a single therapeutic agent for gestational trophoblastic neoplasms. Am J Obstet Gynecol, 150(1):69-75.

[34]TaylorF, GrewT, EverardJ, et al., 2013. The outcome of patients with low risk gestational trophoblastic neoplasia treated with single agent intramuscular methotrexate and oral folinic acid. Eur J Cancer, 49(15):3184-3190.

[35]UbertiEMH, FajardoMDC, da CunhaAGV, et al., 2015. Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women. Rev Bras Ginecol Obstet, 37(6):258-265.

[36]WinterMC, TidyJA, HillsA, et al., 2016. Risk adapted single-agent dactinomycin or carboplatin for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia. Gynecol Oncol, 143(3):565-570.

[37]WongLC, ChooYC, MaHK, 1985. Methotrexate with citrovorum factor rescue in gestational trophoblastic disease. Am J Obstet Gynecol, 152(1):59-62.

[38]WuXD, QinJL, ShenT, et al., 2020. The 16-year experience in treating low-risk gestational trophoblastic neoplasia patients with failed primary methotrexate chemotherapy. J Gynecol Oncol, 31(4):e36.